DESCRIPTION: High density lipoprotein concentrations are known to be important in assessing coronary heart disease risk. Reduction in dietary fat is known to decrease HDL concentrations, but little was known regarding its influence on HDL subfraction distribution. In certain hyperlipidemic states, such as hypertriglyceridemia, HDL concentrations are lower. Thus, one of the central questions of this application is whether diet-induced reduction in HDL will result in similar changes in HDL subfractions compared to subjects who have low HDL due to hyperlipidemia. In the first part of the proposal, HDL subfractions in normolipidemic and hyperlipidemic subjects will be studied and the role of diet-induced HDL changes and their relationship to changes in HDL subfractions will be evaluated. In the second part of the proposal, modulation of the distribution of HDL subfractions and mechanism of HDL formation will be studied using fibroblasts and macrophages in culture. These later studies will take advantage of two-dimensional quantitative electrophoresis to isolate HDL subfractions without centrifugation.